scholarly journals Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients.

1993 ◽  
Vol 177 (6) ◽  
pp. 1623-1631 ◽  
Author(s):  
H DerSimonian ◽  
M Sugita ◽  
D N Glass ◽  
A L Maier ◽  
M E Weinblatt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Cell Expansion ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Major Function ◽  
T Cell Expansion

Rheumatoid arthritis (RA) represents a heterogenous disease characterized by chronic polyarthritis. Most patients with adult RA inherit HLA-DR4 or -DR1 major histocompatibility complex (MHC) genes. While the molecular basis for this genetic predisposition is unknown, the major function of these MHC-encoded molecules is to present peptides to T lymphocytes. It is hypothesized that an endogenous or environmental antigen initiates a MHC-restricted immune response mediated by T lymphocytes, which is followed by a chronic inflammatory reaction involving many cell types. In chronic RA, previous or ongoing antigenic activation might result in detectable skewing of the peripheral alpha/beta T cell receptor (TCR) repertoire. Here we demonstrate a marked expansion of V alpha 12.1-bearing CD8+ T cells in the peripheral blood (mean, 22%; range, 10-43%) of > 15% of RA patients. A major proportion of these patients shared HLA-DQ2 in addition to the expected high frequency DR1 and DR4 alleles. Detailed molecular analysis in three of the RA patients with elevated V alpha 12.1+ T cells identified repeated TCR alpha chain sequences consistent with clonal V alpha 12.1+,CD8+ T cell expansion. In addition to shared TCR V alpha 12.1 germline gene usage among unrelated subjects, a conserved J alpha motif was also detected. Together, these results suggest an antigen-driven mechanism of T cell expansion in these patients and may offer a new approach in examining specific antigen that stimulate T cells in RA.

scholarly journals Expansion of a unique subpopulation of cytotoxic T cells that express a C alpha V delta 1 T-cell receptor gene in a patient with severe persistent neutropenia

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3157-3163
Author(s):  
I Bank ◽  
M Book ◽  
L Cohen ◽  
A Kneller ◽  
E Rosental ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Gene Segment ◽  
Cell Receptor ◽  
Severe Neutropenia ◽  
Pcr Analysis

CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional “hybrid” C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.

Clonal T-cells and monocytosis in cancer patients and relationship to prognosis, and incidence of autoimmunity, fatigue, and second primary malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22038-e22038
Author(s):  
Michael Snyderman ◽  
Judy Mikovits
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Patients ◽  
Cell Expansion ◽  
Positive Impact ◽  
Specific Antigen ◽  
Second Primary ◽  
High Stage ◽  
Stage Disease ◽  
T Cell Expansion

e22038 Background: Clonal T-cell expansion and monocytosis could explain inflammation, fatigue and autoimmunity seen with cancer if both cell types release excess amounts of cytokines and disregulate the immune system. Cytokines can also have a paracrine effect and increase malignant cell proliferation. Methods: 48 patients with various neoplasms from an oncology practice were studied. Myeloid dyscrasias were excluded to allow interpretation of monocytosis. Clonal TCR rearrangements were done in a reference lab. Cancer-Related Fatigue (CRF) data as defined by the NCCN was available in 34 patients. The study was done 2010–2013. Results: See Table. Conclusions: Presence of a clonal T-cell expansion was associated with the greatest likelihood of high stage disease, second malignancy, autoimmunity and CRF. Monocytosis had a similar effect but less than clonal T-cell positivity. The patients with the least likelihood of high stage disease and CRF had no detectable clonal T-cell expansion and no monocytosis. Of the 25 originally negative or undetectable clonal T-cell expansions, 4 became positive 1-2 years later. The clonal T-cell and monocyte proliferation are unlikely to be reactive because a true tumor-specific antigen is rare and because there appeared to be a negative rather than a neutral or positive impact on multiple parameters. Further investigation to determine the subsets of T-cells and monocytes that are expanded and their production of proinflammatory cytokines, etiology of their proliferation and their role in the progression of neoplasia could lead to new treatments to improve the course and prognosis of cancer patients. [Table: see text]

scholarly journals T-cell receptor α enhancer is inactivated in αβ T lymphocytes

2015 ◽  
Vol 112 (14) ◽  
pp. E1744-E1753 ◽  
Author(s):  
Beatriz del Blanco ◽  
Úrsula Angulo ◽  
Michael S. Krangel ◽  
Cristina Hernández-Munain
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Germ Line ◽  
Cell Receptor ◽  
Thymocyte Development ◽  
Enhancer Activity ◽  
Major Function

The Tcra enhancer (Eα) is essential for Tcra locus germ-line transcription and primary Vα-to-Jα recombination during thymocyte development. We found that Eα is inhibited late during thymocyte differentiation and in αβ T lymphocytes, indicating that it is not required to drive transcription of rearranged Tcra genes. Eα inactivation resulted in the disruption of functional long-range enhancer-promoter interactions and was associated with loss of Eα-dependent histone modifications at promoter and enhancer regions, and reduced expression and recruitment of E2A to the Eα enhanceosome in T cells. Enhancer activity could not be recovered by T-cell activation, by forced expression of E2A or by the up-regulation of this and other transcription factors in the context of T helper differentiation. Our results argue that the major function of Eα is to coordinate the formation of a chromatin hub that drives Vα and Jα germ-line transcription and primary rearrangements in thymocytes and imply the existence of an Eα-independent mechanism to activate transcription of the rearranged Tcra locus in αβ T cells.

scholarly journals Biased t cell receptor v gene usage in rheumatoid arthritis. oligoclonal expansion of t cells expressing vα2 genes in synovial fluid but not in peripheral blood

1993 ◽  
Vol 36 (9) ◽  
pp. 1234-1243 ◽  
Author(s):  
Barbara M. Bröker ◽  
Ulf Korthäuer ◽  
Peter Heppt ◽  
Gerd Weseloh ◽  
RÜDiger De La Camp ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Synovial Fluid ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Gene Usage ◽  
V Gene ◽  
Oligoclonal Expansion

scholarly journals Clonally Expanded Bone Marrow T Cells Show Effector Differentiation and Rarely Recognize Disease-Associated Antigens in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Carlotta Welters ◽  
Meng-Tung Hsu ◽  
Christian Alexander Stein ◽  
Livius Penter ◽  
María Fernanda Lammoglia Cobo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Cell Expansion ◽  
Advisory Committees ◽  
Myeloma Cells ◽  
T Cell Expansion

Multiple myeloma is a malignancy of monoclonal plasma cells accumulating in the bone marrow. The critical influence of tumor-infiltrating T cells on disease control and therapeutic responses has been shown in a variety of malignancies, however, the role of multiple myeloma bone marrow-infiltrating T cells is incompletely understood. Although it has been shown that multiple myeloma neo-antigen-specific T cells can be expanded in vitro, little is known about functions and specificities of clonally expanded multiple myeloma-infiltrating bone marrow T cells. Here we asked at the single cell level whether clonally expanded T cells i) were detectable in multiple myeloma bone marrow and peripheral blood, ii) showed characteristic immune phenotypes, and iii) recognized antigens selectively presented on multiple myeloma cells. A total of 6,744 single bone marrow T cells from 13 treatment-naïve patients were index-sorted and sequenced using our methodologies for determination of paired T cell receptor (TCR) αβ sequences along with immune phenotype, transcription factor and cytokine expression. Clonal T cell expansion occurred predominantly within the CD8+ compartment. Phenotypes of clonally expanded T cells were distinctive of cytolytic effector differentiation and significantly different from non-expanded CD8+ T cells. Less than 25% of expanded CD8+ T cell clones expressed the immune checkpoint molecules programmed death-1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), or T cell immunoglobulin and mucin-domain containing-3 (TIM-3), while B and T lymphocyte attenuator (BTLA) was expressed on more than half of the expanded clones. Clonal T cell expansion did not correlate with neo-antigen load as determined by whole exome and RNA sequencing of purified multiple myeloma cells. Furthermore, peripheral blood TCRβ repertoire sequencing from five selected patients with substantial bone marrow T cell expansion identified 90% of expanded bone marrow T cell clones overlapping with peripheral blood. To determine whether clonally expanded bone marrow T cells recognized antigens selectively presented on multiple myeloma cells, 71 dominant TCRs from five selected patients with substantial clonal T cell expansion were re-expressed in 58α-β- T-hybridoma reporter T cells and co-incubated with CD38-enriched multiple myeloma cells from the same patients. Only one of these TCRs recognized antigens selectively presented on multiple myeloma cells and this TCR was not neo-antigen-specific. Hypothesizing that the target antigen was a non-mutated self-antigen, we could show that this TCR also recognized the plasma cell leukemia cell line U-266 in an HLA-A*02:01-restricted manner. In summary, clonally expanded T cells in multiple myeloma bone marrow of newly diagnosed patients show cytolytic effector differentiation. In the majority of patients, clonally expanded bone marrow T cells do not recognize antigens presented on multiple myeloma cells and are not neo-antigen-specific. Our findings are relevant for the design of future therapeutics and clinical trials. The identified TCR, which recognizes a multiple myeloma antigen shared with U-266 in an HLA-A*02:01-restricted manner, could be a promising candidate for T cell therapy. Disclosures Bullinger: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees.

Expansion of a unique subpopulation of cytotoxic T cells that express a C alpha V delta 1 T-cell receptor gene in a patient with severe persistent neutropenia

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3157-3163 ◽  
Author(s):  
I Bank ◽  
M Book ◽  
L Cohen ◽  
A Kneller ◽  
E Rosental ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Gene Segment ◽  
Cell Receptor ◽  
Severe Neutropenia ◽  
Pcr Analysis

Abstract CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional “hybrid” C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.

scholarly journals PILAR is a novel modulator of human T-cell expansion

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1259-1268 ◽  
Author(s):  
Eduardo Huarte ◽  
Juan R. Cubillos-Ruiz ◽  
Yolanda C. Nesbeth ◽  
Uciane K. Scarlett ◽  
Diana G. Martinez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Ex Vivo ◽  
Joint Inflammation ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Human T Cell ◽  
T Cell Expansion ◽  
Inflammatory Synovial Fluid

Abstract Robust T-cell responses without autoimmunity are only possible through a fine balance between activating and inhibitory signals. We have identified a novel modulator of T-cell expansion named proliferation-induced lymphocyte-associated receptor (PILAR). Surface PILAR is markedly up-regulated on CD4 and, to a lesser extent, on CD8 T cells on T-cell receptor engagement. In absence of CD28 costimulation, PILAR signaling through CD161 supports CD3 antibody-dependent and antigen-specificT-cell proliferation by increasing the expression of antiapoptotic Bcl-xL and induces secretion of T helper type 1 cytokines. These effects are abrogated by PILAR blockade with specific antibodies, which decrease surface levels of CD28. In contrast, PILAR induces apoptotic death on naive and early activated T cells if CD161 engagement is blocked. PILAR is expressed by approximately 7% to 10% of CD4 T cells in 2 samples of inflammatory synovial fluid, suggesting a potential role in the pathogenesis of joint inflammation. In addition, in the ovarian cancer microenvironment, effector T cells express PILAR, but not CD161, although expression of both can be augmented ex vivo. Our results indicate that PILAR plays a central role in modulating the extent of T-cell expansion. Manipulation of PILAR signaling may be important for treatment of autoimmune diseases and cancer.

A Murine Xenograft Model for Human T Cell Mediated Graft Versus Host Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4977-4977
Author(s):  
Bruno Nervi ◽  
Michael Rettig ◽  
Julie Ritchey ◽  
Jon Walker ◽  
Gerhard Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Cell Expansion ◽  
Fold Increase ◽  
Host Disease ◽  
Graft Versus Host ◽  
Human T Cell ◽  
T Cell Expansion

Abstract Murine xenograft models of human T cell (HuT) mediated graft-versus-host-disease (GvHD) are of potential value but limited by poor engraftment and low and variable incidence of clinical GvHD even after injection of >108HuT cells. The NOD SCID β2M null mice (β2 mice) lack macrophage activity, T, B and NK cells and represent an improved target for HuT cell expansion and activation compared to other immunodeficient mouse models. To induce GvHD, sublethally irradiated β2 mice were injected intravenously via the tail vein (iv) or retroorbitally (ro) with human peripheral blood mononuclear cells (huPBMC) or purified HuT (98% purity). β2 mice conditioned with 250cGy and injected iv with huPBMC (107T cells;n=4) or HuT (0.5–2x107T cells;n=28) failed to engraft and did not develop GvHD. In contrast, β2 mice conditioned with 250cGy and injected ro with huPBMC (107T cells;n=11) or HuT cells (107;n=14) exhibited 19% HuT engraftment 2–3 weeks post-infusion and developed weight loss (>20%) consistent with lethal GvHD, with an overall survival of 82% and 21%, respectively, at 5 weeks (p=0.006). Addition of IL-2 (3x105 IU IP/TIW) had no effect on T cell expansion or GvHD. FACS analysis demonstrated HuT infiltration in the spleen (46%), liver (60%), lung (49%), kidney (40%), and bone marrow (11%). Histological analysis showed an extensive and diffuse accumulation of immature lymphocytes in the spleen, thymus and lymph nodes, and a perivascular infiltration in the lung, liver, kidney but not in the skin or gut. The immunohistochemestry confirmed that these cells were HuT (human CD45+ and CD3+). Furthermore, we observed a 10–15 fold increase in the expression of T cell activation markers CD25, CD30, and CD69 in both the peripheral blood and tissues, compared with naive T cells or T cells from mice that did not develop GvHD. We also evaluated the levels of various human cytokines in the serum of the β2 mice using a cytometric bead array multiplex assay. On day 10 after the injection of HuT and before the start of any clinical sign of GvHD, mice that went on to develop lethal GvHD had 90 times higher levels of IFNγ in serum (>5000pg/ml) compared to mice that did not develop GVHD (<62 pg/ml) (p=0.003). Interestingly both had nearly identical numbers of HuT/ul in blood (32+39 and 33+41 HuT/ul) on day 10. We also observed a significant increase in human IL-10 levels and TNFα in mice that developed GvHD. Mice that developed lethal GvHD had a 70 fold increase of HuT/ul in the 3rd week (1550 versus 22/ul p<0.003). We improved this model by depletion of murine macrophages using clodronate-containing liposomes (clod) administered iv before the HuT injections. Mice injected with 5x106HuT with clod developed lethal GvHD (3/3) on day 15.7+1.5, with 107HuT (3/3) on day 10.3+5.4 and mice injected with 107HuT without clod on day 13.4+5.4 (8/12)(p<0.05). In contrast, RAG2 γ −/ − mice (RAG2) treated in identical fashion to the β2 mice failed to engraft HuT after both iv and ro injection (350cGy). Both increasing radiation doses (350 to 600cGy) and/or the addition of clod iv resulted in significantly enhanced engraftment of HuT and lethal GvHD. CD4/CD8 ratio of HuT cells expanding in RAG2 mice was <1 in sharp contrast to the β2 mice where the ratio was >2.5. Conclusion: NOD-SCID-β2M null xenotransplant model is uniquely permissive for human T cell expansion after sublethal radiation and may be used as a preclinical platform to study the impact of ex-vivo manipulation and genetic modification of human T cell as GvHD.

Rapid Generation of Antigen-Specific T Cells for Pre-Clinical and Clinical Applications Using a Novel Mini Cell Bioreactor

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 208-208
Author(s):  
Juan F Vera ◽  
Lara Brenner ◽  
Ann M. Leen ◽  
Helen E. Heslop ◽  
Gianpietro Dotti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cell Expansion ◽  
Culture Conditions ◽  
Antigen Specificity ◽  
Permeable Membrane ◽  
T Cell Expansion ◽  
The Impact

Abstract Although flasks, bags, or rocking bioreactors can readily expand T lymphocytes after non-specific stimulation, the requirements for antigen-driven expansion of cytotoxic T lymphocytes (CTLs) are more rigorous. Antigen-specific T cells proliferate optimally only in the 2 mL wells of 24-well plates and cannot reproducibly be adapted to growth in flasks or bags. Hence, preparation of antigen-specific T cells for adoptive immunotherapy of malignancies is extremely time-consuming, requiring between 4wks and 3mths to produce sufficient cells for therapeutic purposes, and expensive (media + plastics + cytokines + man hours). The extensive manipulation required during the culturing process increases the risk of contamination. In combination, these problems obstruct the broader clinical application of antigen-specific T cells. Antigen-specific T cell growth is limited by gas exchange, nutrients and waste buildup. Bioreactors developed to provide these requirements tend to be complex, involving mechanical rocking or stirring and continuous perfusion, which increases the expense of the procedure and limits the number of products to the number of mechanical devices that can be housed and maintained. We have now explored the use of a new static mini Cell Bioreactor for antigen-specific T cell expansion. This device is essentially a flask with a gas permeable membrane supported by a plastic lattice as its base. The O2/CO2 exchange from the base allows large volumes of media to be added thereby reducing nutrient limitations and waste build-up, and consequently the manipulation required to sustain cell expansion. We tested two different sizes of Cell Bioreactor, 10 cm2 and 100 cm2 that hold a maximum of 40mL and 2000mL of media, respectively. We were able to generate and expand Epstein-Barr virus antigen-specific cytotoxic T lymphocytes (EBVCTLs) from normal donors by coculturing antigen presenting cells (APC) (1.4E+05 × cm2) with established EBV-CTL (4.3E+03 × cm2) at an optimized cell density and stimulator: responder ratio (32:1). These culture conditions induced accelerated CTL expansion (42.5 fold ±14.8 vs 3.4 fold ±1.2 within 7 days) without media change. Manipulation was restricted to cytokine addition every 3–4 days and to LCL stimulation on a weekly basis. A single 100cm2 bioreactor could produce up to 800E+06 antigen-specific T cells, which would have required approximately 320 wells in 24 well plates (&gt;13 plates) under standard culture conditions. The CD4:CD8 T cell ratio and phenotype of the Cell Bioreactor-expanded CTLs was similar to those expanded using the conventional method (CD27 48% vs 52.4%, CD28 65.2% vs 62.2%, CD62L 53.15% vs 54.5%, CD45RO 58.1% vs 55.7%, and CD45RA 51.1% vs 54.9%). Antigen specificity, as evaluated by tetramer analysis and IFN-g ELIspot assay demonstrated no significant differences between CTL expanded by each process. Finally, cytolytic function was confirmed using a standard chromium release assay where both sources of CTL had high specific killing of the autologous EBV-transformed LCL targets (85%±12% vs 77%±19%) and minimal killing of allogeneic targets (22%±9% vs 15%±12). In summary, we have successfully utilized the new mini Cell Bioreactor technology to induce optimal in vitro antigen-specific T cell expansion with minimal handling. Future work will evaluate the impact of the accelerated expansion on differentiation and memory markers. This new system is suited to the clinical grade expansion of other cell types including suspension cell lines, and mitogen-activated T cells, as well as T cell blasts engrafted with chimeric antigen receptors.

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